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Europaisches Patentamt
European Patent Office
Office europeen des brevets

0 471 986 B1

EUROPEAN PATENT SPECIFICATION

~ G01N 27/30

(2y Application number: 91112100.2

@ Date of filing: 19.07.91

Divisional application 941 15175.5 filed on
.19/07/91.

Higashikujo

20.07.90 JP 193646/90

Minami-ku

15.07.91 JP 173737/91

Kyoto-shi

@ Date of publication of application:

Kyoto-f u (JP)

26.02.92 Bulletin 92/09

@ Inventor: Nankai, Shiro

4-50-12, Nasuzukuri

Hirakata-shi,

18.10.95 Bulletin 95/42

Osaka-fu (JP)

Inventor: Kawaguri, Mariko

202, 1-12-1, Dainichi-cho

CH DE FR GB IT LI

Moriguchi-shi,

Osaka-fu (JP)

Inventor: Yoshioka, Toshihiko

EP-A- 0 220 888

4-15-11-302, Shinmorl,

EP-A- 0 230 472

Asahi-ku

WO-A-90/00738

Osaka-shi,

DE-A- 3 822 530

Osaka-fu (JP)

US-A-4 713 165

Inventor: Tsutsumi, Haruhiro

1833-1, Tanokubo,

Shigenobu-cho

AL CO., LTD.

Onsen-gun,

1006, Oaza Kadoma

Ehime-ken (JP)

Kadoma-shi,

Osaka-fu, 571 (JP)

Proprietor: KYOTO DAIICHI KAGAKU CO., LTD.

57 Nishiaketa-cho

CD
00

Note: Within nine months from the publication of the mention of the grant of the European patent, any person
may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition
shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee
has been paid (Art. 99(1 ) European patent convention).

Rank Xerox (UK) Business Services

13.10/3.09/3.3-31

EP 0 471 986 B1

Inventor: Terao, Kyozo
1007-10, Kubota-cho,
Kume

Matsuyama-shi,

Ehlme-ken (JP)

Inventor: Tanlmoto, Naokl

1058-15, Shltsukawa,

Shlgenobu-cho

Onsen-gun,

Ehlme-ken (JP)

Inventor: Yoshloka, Masahlro

2-11-4, Hlgashiyosumf-cho

Takatsukl-shl

Osaka-fu (JP)

Inventor: Hyodo, Hiroshi

1640-8, Mlnamlgasa-cho

Kusatsu-shf,

Shiga-ken (JP)

Inventor: Uchigakl, Takatoshl

5, Higashitsukurimichi,

Koaza Kamlkoma,

Oaza

Yamashiro-cho,
Souraku-gun,
Kyoto-fu (JP)

Patentanwalte

von Kreisler, Seltlng, Werner
Postfach 10 22 41
D-50462 Koln (DE)

EP 0 471 986 B1

Description

The present invention relates to a quantitative analyzer for measuring such as a glucose level of
biological fluid, particularly body fluid.
5 Various biosensors utilizing a specific catalytic action possessed by enzymes have recently been
developed and applied, in particular, to clinical field. Development of biosensors having an ability of
providing rapid and yet precise analytical results has long been desired in view of increasing number of
samples and increasing number of items to be tested.

Diabetes mellitus is a disease from which the patient can not be completely recovered. However, the
w patient can live a normal life by keeping a concentration of glucose in blood at a normal level. Accordingly,
constant retention of the normal glucose level is essential as a treatment of diabetes mellitus. The retention
of the normal glucose level may be easily carried out on inpatients under physician's observation.

However, outpatients must conduct self-management in order to keep their blood glucose at a constant
normal level. Such self-management includes dietary therapy, ergotherapy, and drug therapy, and the
/5 patients usually conduct the setf-management on the above-noted two or more items under physician's
directions. It is reported that when patients can check by themselves if their blood glucose level analytical
results of glucose level in blood is within normal range or not, the self-management can be more effective.
In the treatment of insulin-dependent diabetes mellitus (IDDM), normal blood glucose level is main-
. tained through repeated insulin-injections effected by patients themselves. However, the blood glucose level
20 varies rapidly and considerably depending on caloric intake, dietary time, and injection time, and therefore,
it is essential that the patients conduct the measurement of the glucose level by themselves.

Under such circumstances, various portable measurement systems have long been commercially
available, which enable diabetes patients to conduct the glucose level measurement by themselves. Blood
glucose level is generally determined using such a conventional measurement system in the following
25 manner: whole blood which has been taken from a fingertip or ear lobe using a needle is contacted a test
paper containing an enzyme specifically reacting with glucose and a color-producing reagent which
develops color based on oxidation-reduction reaction; thereby the reagent and blood glucose react together
and produce color, thickness of which is measured using an exclusive mini-reflectometer analyser attached
to the system; the blood glucose level is determined on the basis of the calibration curve previously
30 prepared and memorized in the analyzer.

However, it has been found that the blood glucose level determined according to the above systems
varies greatly depending on patients' manipulation for measurement. Accordingly, Diabetes Associations in
many countries have counseled the improvement of the measurement systems. The most important factor
causing the above-noted variation of test results is associated with the manipulation needed for removing
35 excessive blood from the test paper after a predetermined time. The removal of excessive blood is usually
conducted through wiping with absorbent cotton, removing with a filter paper or rinsing with water, and such
procedures bring about test errors in the following manner.

(i) Remaining blood on the test paper due to incomplete removal gives greater value than the real

(ii) Excessive wiping or rinsing damages the test paper or washes out colored reagent, which gives
40 smaller value than the real.

(Hi) Inadequate manipulation which brings about shortage of reaction time causes insufficient coloration of
the reagent, and mistimed manipulation makes it impossible to completely remove blood because of
blood clotting or drying, thereby erroneous test results are obtained.

Moreover, when blood is contacted the test paper, the command (key input) of the timing for starting
45 the measurement should be effected within an elapse of mistiming from ±2 to 3 seconds. In actual cases (of

some patients), however, this mistiming may be 30 seconds to one minute, which can be another factor for

the variation of test results, causing less reliability of measured values.

In the last few years there has been commercially available a new measurement system (manufactured

by Medisense Inc., commodity name: Exactech) which has solved a main part of the above problems. This
50 system is a pen type system which displays measuring results 30 seconds after its measurement start

switch is pressed the moment blood is fed onto its test electrode chip. The system has obviated the need

of removing blood and the factors for considerable test errors.

Diabetics, in some cases, have poor blood circulation and are therefore susceptible to infectious

disease. This means that a slight wound on their hands or feet may cause suppuration, thus requiring the
55 diabetics to keep themselves clean. Accordingly, equipment and a sensor for collecting blood in the

measurement of blood glucose level are preferably provided in disposable form in view of hygienic control

rather than used a plurality of times after they are sterilized and stored. This will ensure safety in hygiene

and alleviate patients' burden.

EP 0 471 986 B1

As a method that allows a sensor to be disposable, a biosensor has already been proposed which is
disclosed in JP-A-6 1-294351. This biosensor, as shown in Fig. 1, is so constructed that electrode systems
136(136'), 137(137'), and 138(138') made of carbon or the like are formed on an insulating substrate 135 by
a method of screen printing or the like, an insulating layer 139 is provided thereon, the electrode systems

5 are covered with a porous body 141 carrying oxidoreductase and electron acceptors, and all these are
integrated with a retaining frame 140 and a cover 142. When a sample liquid is dropped onto the porous
body, the oxidoreductase and electron acceptors carried by the porous body are dissolved in the sample
liquid, causing a reaction to proceed between the enzyme and substrate in the liquid and the electron
acceptors to be reduced. After completion of the reaction, the reduced electron acceptors are electrochemi-

w cally oxidized, and the resulting value of oxidation current is used to determine the concentration of
substrate in the sample liquid.

However, in the Exactech, it is necessary to press the measurement start switch, which causes a defect
that a considerable extent of mistiming in the measurement cannot be prevented. Moreover, its analyzer,
being of pen type, makes its switch formed into one. As a result, since the calibration and adjustment of the

T5 analyzer must be carried out using this switch, the key operation involved has been made more complex
unexpectedly. Also, since blood is placed onto the test electrode chips tipped by the pen and measurement
is conducted without wiping the blood off, the patient is required to keep holding the analyzer during
measurement so that the blood will not spill out. The system has therefore been inconvenient to use for the
patients.

20 A further biological fluid measuring device is known from WOA-90700738. This biological fluid measuring

device comprises a sensor for amperometric detection of specific components of body fluids. However, in

this system the sensor is not disposable.

As described heretofore, since the self-management measurement system of blood glucose level

conventionally available requires patients to conduct the command of starting measurement by themselves,
25 it has been accompanied by such a defect: that correct test results cannot be obtained depending on

patients' manipulation. Moreover, complex key operation has been involved in operation for the calibration

and test of the analyzer.

Conventional disposable systems, on the other hand, have been accompanied by such problems that
test results may vary or that patients are required to distinguish whether a sensor has already been used or
30 not.

It is the object of the present invention to provide a quantitative amperometric analyzing method and a
quantitative analyzing apparatus which facilitate the measuring of a specific component in the biological
body fluid.

This object is solved, according to the invention, with the features of claims 1-3 and 5, respectively.
35 According to the present invention, a calibration and a test of the analyzer can be done without key
operation. Another important advantage of the present invention is to provide such a measurement system
further capable of minimizing the variation of test results.

Using an apparatus in which the command of starting measurement can automatically be effected using
a sensor having a capillary-shaped portion that obviates the need of removing excessive blood for self-
40 measurement of blood glucose level, provides the advantage that the variation of test results can be
minimized.

Now the present invention will be described in detail.

The system of the present invention is used as a set with an exclusive sensor. The exclusive sensor is
a "disposable electrode by the amperometric method," while the system is an "amperometric analyzer
45 which displays the concentration of glucose calculated using a calibration curve from a measured current
value."

In use of the system, with the sensor fitted into a sensor holder of the analyzer, the value of resistance
at the electrode is infinity while blood is not supplied. Accordingly, the analyzer distinguishes that the
sensor has been fitted into the holder, awaiting blood to be supplied.
so When blood is supplied, the resistance value abruptly lowers. The sensor detects this lowering of the
resistance value, and distinguishes that blood has been supplied, making the timer of the analyzer start.
After a specified time, a constant voltage is applied to the sensor, and the resulting current is measured and
converted into a glucose level using a previously set calibration curve, the converted result being displayed
as a measured value.

55 For adjustment of the analyser, when a resistive chip (adjustment chip) having a sensor-like shape with
a constant resistance value is fitted into the holder of the analyzer, it shows the constant resistance value
initially. Accordingly, the analyzer distinguishes that it is not the sensor but an adjustment chip, preparing
for the adjustment of the analyzer. Adjustment chips include an adjustment mode switching chip, an

EP 0 471 986 B1

instrumental error compensating chip, a calibration chip, a test chip, and a unit switching chip.
The instrumental error compensation for the analyzer is carried out in the following manner.
When the adjustment mode switching chip is fitted into the holder of the analyzer, the sensor initially
shows a constant low resistance value within a range assigned to the adjustment mode switching chip.
5 From this fact, the analyzer distinguishes that it is the instrumental error compensating chip, switching the
analyzer to the instrumental error compensation mode.

After adjustment of applied voltage, one of two types of compensating chips having predetermined
different resistance values (R Lt R H ) is fitted into the holder of the analyzer, and the resulting measured value
(Ri) is stored in the memory. Then, the other compensating chip is fitted into the holder and the resulting
w measured value (R 2 ) is stored in the memory; thereafter, a subsequent measured value R n is compensated
as a resistance value R according to the following Scheme 1 :

For calibration of the analyzer, when the calibration chip is fitted into the holder of the analyzer, the
20 sensor initially shows a constant resistance value within a range assigned to the calibration chip. From this
fact, the analyzer distinguishes that it is the calibration chip, judging the type of calibration curve from the
resulting resistance value. Whereas a plurality of types of calibration curves are stored in the analyzer, one
type of calibration curve selected thereamong by the calibration chip is set and this is all of the calibration.
Since the calibration curve differs depending on the production lot of sensors, sensors are supplied with
25 calibration chips corresponding to each lot.

For test of the analyzer, when a test chip is fitted into the holder of the analyzer, the sensor initially
shows a constant resistance value within a range assigned to the test chip. From this fact, the analyzer
distinguishes that it is the test chip, displaying the resistance value as converted into the glucose level. The
operator then distinguishes whether any abnormality exists in the analyzer according thereto. It may also be
30 arranged that a normal range is previously stored in the analyzer so that existence of any abnormality will
be displayed.

For switching of unit in the analyzer, when the unit switching chip is fitted into the holder of the
analyzer, the sensor initially shows a constant resistance value within a range assigned to the unit switching
chip. From this fact, the analyzer distinguishes that it is the unit switching chip, setting a unit corresponding
35 to the resistance value.

When a used sensor is fitted into the holder of the analyzer, the sensor initially shows a low resistance
value because the sensor is made wet by a blood sample, and moreover the value of current flowing
through the sensor will vary with the resistance value gradually varying on account of polarization after a
voltage is applied. Accordingly, the analyzer distinguishes that it is a used sensor on the basis of the
40 elapsed stability of the current value (resistance value), displaying the fact on its display unit.

Further, the analyzer automatically detects that the sensor has been fitted in position into the reacting
state, and interrupts the source of the reaction voltage or the like until the reaction is stabilized. This
enables battery consumption to be suppressed.

According to the present invention, since the reaction voltage is applied after the reaction state is
45 stabilized, variation of test results is minimized.

Furthermore, under the condition of high humidity, some sensors (for example, if its porous body 141
(see Fig. 1) is made of any hygroscopic material) are likely made wet due to humidification even though
unused. The sensor thus initially shows a low resistance value, which further gradually varies on account of
polarization after a voltage is applied. Due to this, the sensor may be mis-decided to be a used sensor. To
so prevent this, the above-noted disposable sensor is further provided with an electrode for detection of liquid
junction so that the so-constructed sensor (see Fig. 6) will show a low resistance value when fitted into the
sensor holder of the analyzer having such a circuit as shown in Fig. 5, and that it checks whether or not any
liquid junction exists at the liquid junction electrode when the resistance value gradually varies, where if any
liquid junction exists, it distinguishes that a used sensor has been fitted, while if not, an unused sensor has
55 been fitted, the sensor awaiting blood for measurement to be supplied.

A contact of the analyzer with the electrode for detection of liquid junction may also be used as the
above-mentioned adjustment chip and test chip.

R *

(1)

EP 0 471 986 B1

Fig. 1 is an exploded perspective view showing an example of the sensor of a conventional measure-
ment system;

Fig. 2 is a perspective view of an embodiment of a measurement system according to the present
invention;

5 Fig. 3 is a perspective view of a sensor used in the measurement system in Fig. 2;

Fig. 4 is a block diagram showing an embodiment of a control unit used in the measurement system in
Fig. 2;

Fig. 5 is a block diagram showing another embodiment of the control unit used in the measurement
system in Fig. 2;

w Fig. 6 is an exploded perspective view showing another example of the sensor used in the measurement
system in Fig. 2;

Fig. 7 is an exploded perspective view showing a further example of the sensor used in the measure-
ment system of the present invention;

Fig. 8 is a perspective view in which the sensor in Fig. 7 is assembled; and
75 Fig. 9 is a block diagram of a control unit used in combination with the sensor in Fig. 7.

A first embodiment of the present invention will be described below with reference to Figs. 2 to 6.
Rg. 2 shows an example of a system according to the present invention. Fig. 2 shows an example of a
sensor to be used in combination with the system of the present invention.

Primary constituents contained in the reagent layer of the sensor are oxidoreductase which is specific
20 for an objective substance in biological body fluid and a redox compound that makes an electron carrier of
the enzyme.

As an example, the reaction measurement principle is described below in the case of measuring
glucose level.

Glucose oxidase (hereinafter referred to as GOD) is used as an oxidase and potassium ferrocyanide is
25 used as a mediator. When a test sample containing glucose is provided and contacted the sensor, an
enzyme reaction occurs between the mediator and the glucose in the presence of GOD as shown in
Scheme 2, whereby potassium ferrocyanide is produced in an amount corresponding to the glucose level.
Then after an elapse of a specified time, a constant voltage is applied across a lead 8 of the sensor through
the circuit used in the present invention. Since the oxidation current obtained therefrom is proportional to
30 the concentration of potassium ferrocyanide produced by the enzyme reaction, i.e. glucose level, the
glucose level in the subject body can be determined by measuring the response current.

3 . GOD
35 D - Glucose + 2Fe(CN) 6 + H 2 0 »

Gluconic acid + 2H + + 2Fe(CN) 6 4 ~

40 2Fe(CN} 6 *~ 2Fe(CN) 6 3 - + 2e (2)

Constant voltage

Fig. 4 shows a preferred embodiment of the present invention.

45 Referring to Fig. 4, the operation of the invention is now explained. First, a sensor 13 is inserted into a
connector 14. When the insertion of the sensor 13 is detected by an electrode insertion detector switch 20,
a switch 21 is closed so that a constant voltage required to obtain a response current is applied across the
terminals of the connector 14 by a battery 15 serving as an applied voltage source. The response current of
the sensor 13 inserted into the connector 14 is converted into a voltage by a current-to-voltage converter

50 16, and further inputted into an A/D converter 17.

A microcomputer 18 receives and reads an output signal from the A/D converter 17 and calculates
gulcose concentration. The sensor 13, enzyme electrode as it is, can be considered to be a type of resistor.
For example, if the resistance value of the sensor 13 is Rs, the amplification resistance of the current-to-
voltage converter 1 6 is Rf , and the applied voltage is E, then the output voltage Eo of the current-to-voltage

55 converter 16 can be determined by the following calculation:

Eo = E + ixRf = E + (E/Rs) x Rf

EP 0 471 986 B1

Without any sample supplied, since the resistance value Rs of the sensor 13 is extremely high and
nearly infinity, the resulting current value i is accordingly extremely low, leading to that the output voltage
Eo of the current-to-voltage converter 16 becomes nearly equal to E (Eo =. E).

On the other hand, with a sample supplied to the sensor 13, since the resistance value Rs of the sensor
5 13 abruptly lowers with the value of Eo abruptly increasing conversely, the subject body can be sucked and
detected by continuously monitoring the output voltage Eo of the current-to-voltage converter 16.

As a result, the measuring timer is automatically started by distinguishing the variation of the output
voltage Eo of the current-to-voltage converter 16 with the aid of the A/D converter 17 using the
microcomputer 18. With this operation, the switch 21 is simultaneously opened and, after an elapse of a
w specified time, closed, thereby allowing a measuring result to be obtained.

In order to adjust the analyzer, there is used an adjustment chip 22 having a shape similar to that of the
sensor 13 and having a very small constant resistance value which is not to be compared with that of a new
sensor (equal to infinity). Since the adjustment chip 22 initially shows a stable, constant voltage when
measured, the microcomputer 18 can identify the adjustment chip 22, which is of various types, from the
15 amount of the voltage.

Adjustment chips 22 include ones for uses of adjustment mode switching, instrumental error com-
pensating, calibration, test, unit switching, and the like. When the chip is distinguished to be an adjustment
mode switching chip, the analyzer is switched into the adjustment mode, the resistance value of the
instrumental error compensating chip is stored, and measured values obtained thereafter are compensated.
20 Normally, the adjustment mode switching chip is used when the analyzer is manufactured or remedied. For
example, when the chip is distinguished to be a calibration chip, the microcomputer 18 automatically
identifies and selects a calibration curve depending on the resistance value (voltage value) out of a plurality
of calibration curves previously stored in the analyzer.

When the chip is distinguished to be a test chip, the microcomputer 18 converts the voltage value into
25 a concentration and displays the result onto a display 2, allowing it to be judged from the amount of the
concentration value whether any abnormality in the equipment exists or not.

When the chip is distinguished to be a unit switching chip, the microcomputer 1 8 changes and converts
the concentration value into each concentration unit (for instance, mg/dl or mmol/L), then displaying it.

Table 1 shows a case of distinguishing calibration chips.

No. of calibration
chip

Resistance
value (KQ)

No. of calibration curve

F-0

F- 1

F-2

F-3 [

F-4

F-5

F-6

' 7

F-7

F-8

F-9

Also, the terminal of the connector can be increased in number in such an arrangement as shown in
Fig. 5, so that a calibration chip or test chip can be inserted into a terminal other than that into which the
sensor 1 3 is inserted.

However, it is possible that if the identification of calibration chips and test chips is done merely
depending on the amount of the resistance value, the chip may be mis-distinguished to be a calibration chip
or test chip even when a used sensor is mis-inserted. This is caused by the fact that the resistance value of
a used sensor is so low that it may be of the same level as those of the calibration and test chips.

To prevent this misidentification, the following method is adopted: Voltage value Eoi is measured at the
time point when power supply is turned ON with any electrode inserted into a connector of the system, and
the voltage value E02 is measured once more after the succeeding several seconds. The resulting rate of
voltage change AE is calculated and if it shows a change in voltage above a specified level, the chip is
distinguished to be a used sensor, which is displayed on the display unit. Otherwise, the chip is
distinguished to be a calibration chip or a test chip.

EP 0 471 986 B1

(3)

If the sensor, even though unused, has a property showing behavior similar to that of a used sensor
due to humidification under high humidity condition, electrodes 9a, 9b for detection of liquid junction are
provided in combination with the sensor, as shown in Fig. 6. When the above-noted used sensor is
subjected to discrimination using both this sensor provided with electrodes for detection of liquid junction

10 and the circuit shown in Fig. 5, it is distinguished that if the resistance value between the electrodes for
detection of liquid junction 9a and 9b is infinity, there is no liquid junction, with such a decision made by the
electrodes inserted into the connector that the sensor is an unused one, while if the resistance value
between the electrodes for detection of liquid junction is low, the sensor is a used one. Meanwhile, the A/D
converter 17 is used in combination by turning ON and OFF the switches 21, 21' through the microcom-

15 puter 18.

Rg. 7 is a detailed exploded perspective view of the sensor of the measurement system, which is a
second embodiment of the present invention, and Fig. 8 is an outline perspective view of the same.

On a substrate plate 31 there are provided counter electrode 34 and a measuring electrode 35, leads
33, 32 connected thereto, and an insulating layer 36. Also, although not shown, there is formed a reaction
20 layer containing an enzyme and a mediator so as to cover the counter electrode and measuring electrode.
On the substrate plate 31 there is fixed a cover 39 with a spacer 37 interposed therebetween. Numeral 38
denotes a sample supply hole, through which a sample liquid, i.e. a sample is introduced onto the counter
electrode 34 and measuring electrode 35 by capillarity phenomenon. Reference numeral 40 denotes an air
hole. In order not to mistake the front and back of the sensor, there is provided an inverse-insertion
25 preventing protrusion 41 so as to protrude from one side end of the sensor, whereby the sensor correctly
directed up and down will properly be set with the inverse-insertion preventing protrusion passing through a
counter gap of a connector 51, while the sensor, inversely set, will not be inserted into the connector 51
with an obstacle of the inverse-insertion preventing protrusion 41.

Rg. 9 is a block diagram of the control unit of a measurement system embodying the present invention.
30 Rrst of all, the whole system is thrown into the standby state, starting up a CPU 50.

When the sensor 30 is inserted into the connector 51 of the main unit of the system, a detector circuit
52 detects the insertion of the sensor, turning on a current-to-voltage converter 53, an A/D converter 54, a
temperature sensor 55, and other components through the CPU 50.

Next, when a sample liquid is supplied to the sensor so as to short-circuit the measuring electrode 35
35 and the counter electrode 34 with each other, the resistance value will vary to a great extent. The variation
is distinguished by the CPU 50 through the A/D converter 54, turning off the current-to-voltage converter 53
with the result that no reaction voltage is supplied. Then, the reaction between the enzyme and sample
liquid is allowed to proceed for approximately 55 seconds. During this period, the countdown state is
displayed on an LCD display 56. Thereafter, a reaction voltage is applied for approximately 5 seconds, and
40 the current is measured. This measured value is also displayed on the LCD display 56.

The voltage of a battery 57 is checked by the CPU 50 through a battery checker 58 for each one
sequence of measurement, so that the voltage, if lower than a specified level, will be displayed onto the
LCD display 56. A buzzer indicated by numeral 59 notifies that the sensor 30 has been inserted. An
oscillator 60 generates pulses for clocking the operation of the system.
45 A memory 61 for storing compensation values for each system serves to compensate the variation
among systems. Reference numeral 62 denotes a voltage regulator circuit. A circuit 63 serves to set a
reaction voltage to be applied to the sensor. A circuit 64 serves to reset the CPU when, for example,
measurement is stopped on its way or a battery is changed. A circuit 65 is a gain control circuit.

Although in the above-described embodiments the measurement system is normally in the standby
so state so that the actions such as applying a reaction voltage are not started until the sensor is inserted into
the system main unit, thereby minimizing the number of parts of the system, the present invention is not
limited to such an arrangement and allows another such that a standby switch is provided separately.

As described heretofore, according to the present invention, the introduction of samples can automati-
cally be detected and, further, stable measurement with less variation of its results can be realized.

EP 0 471 986 B1

Claims

1. A quantitative amperometric analyzing method for measuring a specific component in biological body
fluid using a disposable sensor (13) being mounted on an analyzing apparatus, comprising the step of
automatically distinguishing whether a chip (13,22,23) mounted onto a sensor mounting portion (14) of
said analyzing apparatus is a sensor (13) for measuring a test sample or an adjustment chip (22) made
up of a fixed resistor, depending on the value of current flowing through the analyzing apparatus when
said chip (13,22,23) is mounted thereon.

2. A quantitative analyzing apparatus for measuring a specific component in biological body fluid by an
amperometric method using a disposable sensor (13), comprising means for automatically distiguishing
whether a chip (13,22,23) mounted onto a sensor mounting portion (14) of said apparatus is a sensor
(13) for measuring a test sample or an adjustment chip (22) made up of a fixed resistor, depending on
the value of current flowing through the analyzing apparatus when said chip (13,22,23) is mounted
thereon.

a A quantitative amperometric analyzing method for measuring a specific component in biological body
fluid using a disposable sensor (13) being mounted on an analyzing apparatus, comprising the step of
automatically distinguishing whether a sensor (13) mounted onto a sensor mounting portion (14) of said
apparatus is a used one or not, depending on stability of the current value of said sensor (13).

4. A quantitative analyzing method as claimed in claim 3, wherein said disposable sensor (13) is provided
with an electrode for detecting liquid junction, the output of the electrode being used to determine the
stability of the current value.

5. A quantitative analyzing apparatus for measuring a specific component in biological body fluid by an
amperometric method using a disposable sensor, comprising means for automatically distinguishing
whether a sensor (13) mounted onto a sensor mounting portion (14) of said apparatus is a used one or
not, depending on stability of the current value of said sensor (13).

6. A quantitative analyzing apparatus as claimed in claim 5, wherein said disposable sensor (12) is
provided with an electrode for detecting liquid junction, the output of the electrode being used to
determine the stability of the current value.

Patentanspruche

1. Quantitatives amperometrisches Analyseverfahren zum Messen einer bestimmten Komponente in
biologischem Korperfluid mittels eines an einer Analysevorrichtung montierten Einweg-Sensors (13), mit
dem Schritt des automatischen Unterscheidens, ob ein an einem Sensoraufnahmeteil (14) der Analyse-
vorrichtung montierter Chip (13,22,23) ein Sensor (13) zum Messen einer Testprobe oder ein aus einem
festen Widerstand gefertigter Einstellchip (22) ist, und zwar abhangig von dem Wert des Stroms, der
durch die Analysevorrichtung fliefit, wenn der Chip (13,22,23) an dieser montiert ist.

2. Quantitative Analysevorrichtung zum Messen einer bestimmten Komponente in biologischem Korper-
fluid durch ein amperometrisches Verfahren mittels eines Einweg-Sensors (13), mit einer Einrichtung
zum automatischen Unterscheiden, ob ein an einem Sensoraufnahmeteil (14) der Vorrichtung montierter
Chip (13,22,23) ein Sensor (13) zum Messen einer Testprobe oder ein aus einem festen Widerstand
gefertigter Einstellchip (22) ist. und zwar abhangig von dem Wert des Stroms, der durch die
Analysevorrichtung flieBt, wenn der Chip (13,22,23) an dieser montiert ist.

3. Quantitatives amperometrisches Analyseverfahren zum Messen einer bestimmten Komponente in
biologischem Korperfluid mittels eines an einer Analysevorrichtung montierten Einweg-Sensors (13), mit
dem Schritt des automatischen Unterscheidens, ob ein an einem Sensoraufnahmeteil (14) der Vorrich-
tung montierter Sensor (13) ein benutzter Sensor ist oder nicht, und zwar abhangig von der Stabilitat
des Stromwertes des Sensors (13).

4. Quantitatives Analyseverfahren nach Anspruch 3, bei dem der Enweg-Sensor (13) mit einer Elektrode
zum Detektieren einer Flussigkeitsbrucke versehen ist, wobei das Ausgangssignal der Elektrode zum

EP 0 471 986 B1

Bestimmen der Stabilitat des Stromwertes verwendet wird.

5. Quantitative Analysevorrichtung zum Messen einer bestimmten Komponente in biologischem Korper-
fluid durch ein amperometrtsches Verfahren mittels eines Einweg-Sensors, mit einer Einrichtung zum

5 automatischen Unterscheiden, ob ein an einem Sensoraufnahmeteil (14) der Vorrichtung montierter
Sensor (13) ein benutzter Sensor ist Oder nicht, und zwar abhangig von der Stabilitat des Stromwertes
des Sensors (13).

6. Quantitative Analysevorrichtung nach Anspruch 5, bei dem der Einweg-Sensor (12) mit einer Elektrode
to zum Detektieren einer ROssigkeitsbrucke versehen ist, wobei das Ausgangssignal der Elektrode zum

Bestimmen der Stabilitat des Stromwertes verwendet wird.

Revendicatlons

75 1. Procede d'analyse quantitative amperemetrique pour mesurer un constituant sp^cifique dans un fluide
corporel biologique, moyennant I'utilisation d'un capteur jetable (13) monte sur un appareil d'analyse,
comprenant I'etape consistant a determiner de fagon automatique si une microplaquette (13,22,23)
montee sur une partie (14), prevue pour ie montage du capteur, sur ledit appareil d'analyse est un
capteur (13) servant h mesurer un echantillon d'essai ou une microplaquette d'ajustement (22)

20 constitute par une resistance fixe, en fonction de la valeur du courant circulant dans I'appareil
d'analyse, lorsque ladite microplaquette (13,22,23) est montee sur I'appareil.

2. Appareil d'analyse quantitative pour la mesure d'un constituant sptcifique dans un fluide corporel
biologique au moyen d'un procede amperemetrique utilisant un capteur jetable (13), comprenant des

25 moyens pour determiner de facon automatique si une microplaquette (13,22,23) montee sur une partie
(14), prtvue pour le montage du capteur, sur ledit appareil est un capteur (13) servant a mesurer un
echantillon d'essai ou une microplaquette d'ajustement (22) constitute par une resistance fixe, en
fonction de la valeur du courant circulant dans I'appareil d'analyse lorsque ladite microplaquette
(13,22,23) est montee sur I'appareil.

3. Procede d'analyse quantitative amperemetrique pour mesurer un constituant sptcifique d'un fluide
corporel biologique moyennant I'utilisation d'un capteur jetable (13) monte sur un appareil d'analyse,
comprenant I'etape consistant a determiner automatiquement si un capteur (13) monte* sur une partie
(14), prevue pour le montage du capteur, dudit appareil d'analyse, est utilise ou non, en fonction de la

35 stability de ia valeur du courant dudit capteur (13).

4. Proctde d'analyse quantitative selon ia revendication 3, selon lequei ledit capteur jetable (13) est
§quipe d'une electrode pour detecter la jonction de liquide, le signal de sortie de reiectrode etant
utilise pour determiner la stability de la valeur du courant.

5. Appareil d'analyse quantitative pour la mesure d'un constituant specifique d'un fluide corporel biologi-
que au moyen d'un procede amperemetrique utilisant un capteur jetable, comprenant des moyens pour
distinguer automatiquement si un capteur (13) monte sur une partie (14), prevue pour le montage du
capteur, dudit appareil est utilise ou non, en fonction de la stabilite de la valeur du courant dudit

45 capteur (13).

6. Appareil d'analyse quantitative selon la revendication 5, dans iequel ledit capteur (13) est pourvu d'une
electrode servant a detecter une jonction de liquide, le signal de sortie de reiectrode etant utilise pour
determiner la stabilite de ia valeur du courant.

EP 0 471 986 B1

Fig. I

EP 0 471 986 B1

Fig. 2

BP 0 471 986 B1

EP 0 471 986 B1

Fig. 6

10 9b 9a 7 6

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Fig. 7

Fig. 8

lead 32

substrate 31 j 7 spacer 40
plote 41 inverse -insertion

preventing protrusion

EP0 471 986 B1

ox:

- o

connector

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